Liston Group

Liston Group
Liston Group

Research Summary

The Liston laboratory works on regulatory T cells. These are a type of white blood cell that act to suppress the rest of the immune response, preventing spontaneous autoimmune disease and acting as a rheostat to control just how active our immune system is. The number of these cells in our blood goes up as we get old, which may contribute to the immune-suppressed state of older persons. We seek to understand these cells, using both patient material and mouse models, so that we can harness their power to fine-tune the immune system for healthy ageing.
 

Latest Publications

Spaan AN, Neehus AL, Laplantine E, Staels F, Ogishi M, Seeleuthner Y, Rapaport F, Lacey KA, Van Nieuwenhove E, Chrabieh M, Hum D, Migaud M, Izmiryan A, Lorenzo L, Kochetkov T, Heesterbeek DAC, Bardoel BW, DuMont AL, Dobbs K, Chardonnet S, Heissel S, Baslan T, Zhang P, Yang R, Bogunovic D, Wunderink HF, Haas PA, Molina H, Van Buggenhout G, Lyonnet S, Notarangelo LD, Seppänen MRJ, Weil R, Seminario G, Gomez-Tello H, Wouters C, Mesdaghi M, Shahrooei M, Bossuyt X, Sag E, Topaloglu R, Ozen S, Leavis HL, van Eijk MMJ, Bezrodnik L, Blancas Galicia L, Hovnanian A, Nassif A, Bader-Meunier B, Neven B, Meyts I, Schrijvers R, Puel A, Bustamante J, Aksentijevich I, Kastner D, Torres VJ, Humblet-Baron S, Liston A, Abel L, Boisson B, Casanova JL Immunology

The molecular basis of interindividual clinical variability upon infection with is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients present episodes of life-threatening necrosis, typically triggered by infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but TNF-receptor NF-κB-signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts-but not leukocytes-facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor α-toxin. Naturally elicited antibodies against α-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to α-toxin in non-leukocytic cells.

+view abstract Science, PMID: 35587511 19 May 2022

Denton AE, Dooley J, Cinti I, Silva-Cayetano A, Fra-Bido S, Innocentin S, Hill DL, Carr EJ, McKenzie ANJ, Liston A, Linterman MA Immunology

The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center (GC) response, which generates long-lived antibody-secreting cells that protect against (re)infection. Despite intensive investigation, the primary cellular defect underlying impaired GCs in aging has not been identified. Here, we used heterochronic parabiosis to demonstrate that GC formation was dictated by the age of the lymph node (LN) microenvironment rather than the age of the immune cells. Lymphoid stromal cells are a key determinant of the LN microenvironment and are also an essential component underpinning GC structure and function. Using mouse models, we demonstrated that mucosal adressin cell adhesion molecule-1 (MAdCAM-1)-expressing lymphoid stromal cells were among the first cells to respond to NP-KLH + Alum immunization, proliferating and up-regulating cell surface proteins such as podoplanin and cell adhesion molecules. This response was essentially abrogated in aged mice. By targeting TLR4 using adjuvants, we improved the MAdCAM-1 stromal cell response to immunization. This correlated with improved GC responses in both younger adult and aged mice, suggesting a link between stromal cell responses to immunization and GC initiation. Using bone marrow chimeras, we also found that MAdCAM-1 stromal cells could respond directly to TLR4 ligands. Thus, the age-associated defect in GC and stromal cell responses to immunization can be targeted to improve vaccines in older people.

+view abstract Science immunology, PMID: 35522725 06 May 2022

Willemsen M, Van Nieuwenhove E, Seyed Tabib NS, Staels F, Schrijvers R, De Somer L, Liston A, Humblet-Baron S, Wouters C Immunology

No abstract available

+view abstract Rheumatology advances in practice, PMID: 35368972 2022

Group Members

Adrian Liston

Group Leader

Magda Ali

PhD Student

Meryem Aloulou

Visiting Scientist

Samira Benadda

Visiting Scientist

Pascal Bielefeld

Visiting Scientist

Orian Bricard

Postdoc Research Scientist

Oliver Burton

Senior Postdoctoral Scientist

Francine Chenou

Visiting Scientist

Amy Dashwood

PhD Student

James Dooley

Senior Staff Scientist

Vaclav Gergelits

Postdoc Research Scientist

Keith Harrison

Visiting Student

Lubna Kouser

Postdoc Research Scientist

Miroslav Kratochvil

Visiting Scientist

Stephanie Lienart

Research Fellow

Ntombizodwa Makuyana

PhD Student

Alena Moudra

Postdoc Research Scientist

Samar Tareen

Visiting Scientist

Emily Thomas

Visiting Student

Daria Vdovenko

Visiting Scientist

Rafael Valente Veiga

Postdoc Research Scientist